The Comprehensive Cancer Center of Wake Forest University (CCCWFU) serves a large region in western North Carolina and contiguous regions in six adjoining states. In the last grant period, overall peer-reviewed cancer funding increased from $26 to $31 million (direct) and NCI funding increased from $12.2 to $17.7 million. Our NCI funding has increased 3.5 fold since 2000. Notable achievements include: Interdisciplinary and transdisciplinary interactions: Interprogrammatic and intraprogrammatic publications comprise 22% and 37% of publications in the Cellular Damage and Defense Program (CDD), 24% and 21% of those in the Cell Growth and Survival Program (COS), 22% and 40% in the Cancer Prevention and Control Program (CPC), and 22% and 22% of publications in the Clinical Research Program (CRP). Further, in 67%) of the peer-reviewed research grants in Summary II, CCCWFU principal investigators collaborate with other Cancer Center members as co-investigators or consultants These collaborative efforts are at highest levels since our Cancer Center began collecting these metrics. Innovative translational investigations: From our own preclinical science, we developed a portfolio of therapeutic and imaging clinical investigations. We also initiated nationally prominent programs in prostate cancer genetics, and, using our NCI-funded CCOP research base, led large-scale clinical trials in symptom management. Quality scientific contributions: Whether measured by high impact publications, NCI funding, or indisputably important contributions to cancer science and cancer care, CCCWFU investigators made important contributions to the national cancer effort. Support is requested for Cancer Center Support Grant for Years 37 through 41. The Center has four Programs: Cell Growth and Survival, Cellular Damage and Defense, Clinical Research, and Cancer Prevention and Control. Support is also requested for 9 shared resources: Bioanalytical Laboratory, Biostatistics, Cell and Viral Vector Core Laboratory, Cellular Imaging, Clinical Research Management, Crystallography and Computational Biosciences, Flow Cytometry, Microarray, and Tumor Tissue. For the next funding cycle, we have carefully crafted a strategic plan to reduce the burden of cancer in our region and in the nation.